Impact of Treatment with Direct Antivirals on Coagulation Parameters in Patients with Hepatitis C Virus-Related Liver Cirrhosis and Sustained Virological Response.

Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.

Correlations between Retinal Arterial Morphometric Parameters and Neurodegeneration in Patients with Type 2 Diabetes Mellitus with No or Mild Diabetic Retinopathy.

Background and Objectives: In patients with diabetes mellitus (DM), the neural retina is starting to degenerate before the development of vascular lesions. Our purpose was to investigate the correlation between the retinal arterial morphometric parameters and structural neurodegeneration in patients with type 2 DM with no or mild diabetic retinopathy (DR). Materials and Methods: This is a prospective study including 53 eyes of patients with type 2 DM and 32 eyes of healthy controls. Based on SD-OCT (spectral domain-optical coherence tomography) images, using a micro-densitometry method, we measured the outer and luminal diameter of retinal arteries and calculated the AWT (arterial wall thickness), WLR (wall-to-lumen ratio), and WCSA (wall cross-sectional area). GCL (ganglion cell layer) and RNFL (retinal nerve fiber layer) thickness were analyzed in correlation with the retinal arterial morphometric parameters mentioned above. Results: GCL was thinner in the inner quadrants in the NDR (no DR) group compared to controls (p < 0.05). RAOD (retinal artery outer diameter), RALD (retinal artery lumen diameter), AWT, WLR, and WCSA were similar between groups. A regression model considering age, gender, duration of DM, and HbA1C was carried out. Central GCL thickness was correlated positively with RAOD (coefficient 0.360 per µm, p = 0.011), RALD (coefficient 0.283 per µm, p = 0.050), AWT (coefficient 0.304 per µm, p = 0.029), and WCSA (coefficient 3.90 per µm, p = 0.005). Duration of DM was positively correlated with WCSA (coefficient 0.311 per one year duration of diabetes, p = 0.043). Conclusions: Significant GCL thinning in the inner quadrants preceded the morphological retinal arterial morphometric changes, supporting the neurodegeneration as primary pathogenic mechanism in DR.

Bilateral simultaneous acute angle closure attack triggered by an over-the-counter flu medication.

Most of the rare bilateral acute angle closure (AAC) cases are precipitated by systemic factors, such as drug intake, snake bite or general anaesthesia. We present a case of simultaneous bilateral AAC in a middle-aged male, precipitated by the use of medication for flu, containing an alpha-1 adrenergic receptor agonist and an anticholinergic agent. In our case, axial length was shorter, anterior chamber depth was narrower, and the lens was thicker than normal, including the patient within the risk group for AAC. In this circumstance, drugs acted as triggers. Case description and evolution following treatment are completed with the discussion of mechanisms involved in triggering bilateral AAC in predisposed patients, as emerging from literature. This case report brings up the risk of bilateral AAC in patients at risk, of which ophthalmologists, physicians of other specialties and patients should be aware of.

A Qualitative Evaluation of ChatGPT4 and PaLM2's Response to Patient's Questions Regarding Age-Related Macular Degeneration.

Patient compliance in chronic illnesses is essential for disease management. This also applies to age-related macular degeneration (AMD), a chronic acquired retinal degeneration that needs constant monitoring and patient cooperation. Therefore, patients with AMD can benefit by being properly informed about their disease, regardless of the condition's stage. Information is essential in keeping them compliant with lifestyle changes, regular monitoring, and treatment. Large language models have shown potential in numerous fields, including medicine, with remarkable use cases. In this paper, we wanted to assess the capacity of two large language models (LLMs), ChatGPT4 and PaLM2, to offer advice to questions frequently asked by patients with AMD. After searching on AMD-patient-dedicated websites for frequently asked questions, we curated and selected a number of 143 questions. The questions were then transformed into scenarios that were answered by ChatGPT4, PaLM2, and three ophthalmologists. Afterwards, the answers provided by the two LLMs to a set of 133 questions were evaluated by two ophthalmologists, who graded each answer on a five-point Likert scale. The models were evaluated based on six qualitative criteria: (C1) reflects clinical and scientific consensus, (C2) likelihood of possible harm, (C3) evidence of correct reasoning, (C4) evidence of correct comprehension, (C5) evidence of correct retrieval, and (C6) missing content. Out of 133 questions, ChatGPT4 received a score of five from both reviewers to 118 questions (88.72%) for C1, to 130 (97.74%) for C2, to 131 (98.50%) for C3, to 133 (100%) for C4, to 132 (99.25%) for C5, and to 122 (91.73%) for C6, while PaLM2 to 81 questions (60.90%) for C1, to 114 (85.71%) for C2, to 115 (86.47%) for C3, to 124 (93.23%) for C4, to 113 (84.97%) for C5, and to 93 (69.92%) for C6. Despite the overall high performance, there were answers that are incomplete or inaccurate, and the paper explores the type of errors produced by these LLMs. Our study reveals that ChatGPT4 and PaLM2 are valuable instruments for patient information and education; however, since there are still some limitations to these models, for proper information, they should be used in addition to the advice provided by the physicians.

Visual outcomes and prognostic factors following 23G vitrectomy for vitreous hemorrhage in eyes with proliferative diabetic retinopathy.

PURPOSE: We aimed to evaluate the factors influencing the visual gain following pars plana vitrectomy for vitreous hemorrhage in patients with proliferative diabetic retinopathy. METHODS: A retrospective study was conducted on 172 eyes of 143 consecutive patients with diabetes mellitus between January 2012 and January 2018. Demographic data, ophthalmological findings, surgery details, and visual outcomes were gathered after consulting the patients' records. The main outcome measured was the improvement of best corrected visual acuity and the secondary outcomes measured were rebleeding and complications. RESULTS: Best corrected visual acuity improved in 103 eyes (59.88%), worsened in 45 eyes (26.16%), and remained unchanged in 24 eyes (13.95%). Type 2 diabetes mellitus was significantly associated with better final best corrected visual acuity (p=0.0244). Previous treatment by pan-retinal laser photocoagulation or intravitreal bevacizumab determined better final best corrected visual acuity, but not significantly (p>0.05). Preoperative rubeosis iridis and neovascular glaucoma did not influence the outcomes. The lack of fibrovascular proliferation requiring dissection was a significant factor for better final best corrected visual acuity (p=0.0006). Rebleeding occurred in 37.1% of the eyes and it was not influenced by the antiplatelet drugs (p>0.05). Postoperative neovascular glaucoma was a negative prognostic factor (p=0.0037). CONCLUSION: The final best corrected visual acuity was influenced positively by type 2 diabetes mellitus and the absence of preoperative extensive fibrovascular proliferation and negatively by postoperative neovascular glaucoma.

Advanced ImageJ Analysis in Degenerative Acquired Vitelliform Lesions Using Techniques Based on Optical Coherence Tomography.

Acquired vitelliform lesions (AVLs) are associated with a large spectrum of retinal diseases, among which is age-related macular degeneration (AMD). The purpose of this study was to characterize AVLs' evolution in AMD patients using optical coherence tomography (OCT) technology and ImageJ software. We measured AVLs' size and density and followed their impacts over surrounding retinal layers. Average retinal pigment epithelium (RPE) thickness in the central 1 mm quadrant (45.89 ± 27.84 µm vs. 15.57 ± 1.40 µm) was significantly increased, as opposed to the outer nuclear layer (ONL) thickness, which was decreased (77.94 ± 18.30 µm vs. 88.64 ± 7.65 µm) in the vitelliform group compared to the control group. We found a continuous external limiting membrane (ELM) in 55.5% of the eyes compared to a continuous ellipsoid zone (EZ) in 22.2% of the eyes in the vitelliform group. The difference between the mean AVLs' volume at baseline compared to the last visit for the nine eyes with ophthalmologic follow-up was not statistically significant (p = 0.725). The median follow-up duration was 11 months (range 5-56 months). Seven eyes (43.75%) were treated with intravitreal anti-vascular endothelium growth factor (anti-VEGF) agent injections, in which we noted a 6.43 ± 9 letter decrease in the best-corrected visual acuity (BCVA). The increased RPE thickness could suggest hyperplasia contrary to the decreased ONL, which could mirror the impact of the vitelliform lesion on photoreceptors (PR). Eyes that received anti-VEGF injections did not show signs of improvement regarding BCVA.

The Predictive Capabilities of Artificial Intelligence-Based OCT Analysis for Age-Related Macular Degeneration Progression-A Systematic Review.

The era of artificial intelligence (AI) has revolutionized our daily lives and AI has become a powerful force that is gradually transforming the field of medicine. Ophthalmology sits at the forefront of this transformation thanks to the effortless acquisition of an abundance of imaging modalities. There has been tremendous work in the field of AI for retinal diseases, with age-related macular degeneration being at the top of the most studied conditions. The purpose of the current systematic review was to identify and evaluate, in terms of strengths and limitations, the articles that apply AI to optical coherence tomography (OCT) images in order to predict the future evolution of age-related macular degeneration (AMD) during its natural history and after treatment in terms of OCT morphological structure and visual function. After a thorough search through seven databases up to 1 January 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 1800 records were identified. After screening, 48 articles were selected for full-text retrieval and 19 articles were finally included. From these 19 articles, 4 articles concentrated on predicting the anti-VEGF requirement in neovascular AMD (nAMD), 4 articles focused on predicting anti-VEGF efficacy in nAMD patients, 3 articles predicted the conversion from early or intermediate AMD (iAMD) to nAMD, 1 article predicted the conversion from iAMD to geographic atrophy (GA), 1 article predicted the conversion from iAMD to both nAMD and GA, 3 articles predicted the future growth of GA and 3 articles predicted the future outcome for visual acuity (VA) after anti-VEGF treatment in nAMD patients. Since using AI methods to predict future changes in AMD is only in its initial phase, a systematic review provides the opportunity of setting the context of previous work in this area and can present a starting point for future research.

SD-OCT Biomarkers and the Current Status of Artificial Intelligence in Predicting Progression from Intermediate to Advanced AMD.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the Western World. Optical coherence tomography (OCT) has revolutionized the diagnosis and follow-up of AMD patients. This review focuses on SD-OCT imaging biomarkers which were identified as predictors for progression in intermediate AMD to late AMD, either geographic atrophy (GA) or choroidal neovascularization (CNV). Structural OCT remains the most compelling modality to study AMD features related to the progression such as drusen characteristics, hyperreflective foci (HRF), reticular pseudo-drusen (RPD), sub-RPE hyper-reflective columns and their impact on retinal layers. Further on, we reviewed articles that attempted to integrate biomarkers that have already proven their involvement in intermediate AMD progression, in their models of artificial intelligence (AI). By combining structural biomarkers with genetic risk and lifestyle the predictive ability becomes more accurate.

Controversy of indomethacin eye drops in the treatment of rheumatoid arthritis-induced corneal ulceration: a case report.

BACKGROUND: Perforation of the cornea is a rare finding in patients with rheumatoid arthritis (RA). Addressing a perforated cornea associated with RA is challenging, since its pathogenesis is not fully elucidated. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) were developed to prevent cystoid macular edema following cataract surgery in patients at risk. Their prescription in inflammation of the anterior segment of the eye may induce negative effects on the ocular surface. We bring into focus a corneal perforation in a patient with RA who used indomethacin eye drops to treat corneal ulceration, but responded promptly to drug discontinuation and initiation of topical cyclosporine 0.1%. Our aim is to emphasize two issues: the contraindication of topical indomethacin in corneal defects, and the immediate positive impact of topical cyclosporine 0.1% on corneal healing. CASE PRESENTATION: A 73-year-old Caucasian woman with a 13-year history of RA was treated for corneal ulceration in her oculus sinister (OS) with topical indomethacin and gentamicin. The patient was being treated with systemic immunosuppression and NSAIDs for the underlying RA and artificial tears in both eyes. No bandage contact lens was used. After 3 weeks of treatment, perforation of the left cornea occurred and the patient was referred to our hospital. Upon admission, visual acuity (VA) in the OS was 20/630. Slit lamp examination of the OS revealed paracentral corneal perforation, iris plugging the perforation site, shallow anterior chamber, clear aqueous humor, and clear lens. Anterior segment optical coherence tomography showed the inclavated iris in the perforation site and minimum corneal thickness of 101 µm. Topical NSAIDs were discontinued and topical treatment was initiated with tobramycin, tropicamide 1%, phenylephrine 10%, and artificial tears five times a day, and occlusive patch. For 5 days, there was no improvement, so topical cyclosporine 0.1% was started, one drop every evening. Within 7 days, the cornea had healed, the iris was liberated from the perforation site, the minimum corneal thickness increased to 250 µm, VA improved to 20/25, and the patient was free of symptoms. CONCLUSIONS: The main "takeaway" lessons from this case are that topical indomethacin should not be prescribed in cases of inflammation of the anterior segment of the eye, and that topical cyclosporine was efficacious in healing corneal perforation in our patient.

Analysis of the Choroid and Its Relationship with the Outer Retina in Patients with Diabetes Mellitus Using Binarization Techniques Based on Spectral-Domain Optical Coherence Tomography.

(1) Background: We aimed to reveal the relationship between the choroid and the outer retina with optical coherence tomography (OCT) in patients with diabetes mellitus (DM) with mild or no diabetic retinopathy (DR) in order to find early biomarkers for progressing retinopathy. (2) Methods: We performed a prospective study including 61 eyes of patients with type 1 or type 2 DM and 36 eyes of healthy controls. All subjects were imaged with Spectralis OCT. The choroid was assesseed using enhanced depth imaging OCT (EDI-OCT). Binarization of subfoveal choroidal images was done with public domain software, ImageJ (version 1.53a; National Institutes of Health, Bethesda, Maryland, USA). (3) Results: Luminal area, stromal area and total choroidal area were significantly decreased in diabetic patients compared to control: 0.23 ± 0.07 vs. 0.28 ± 0.08, p = 0.012; 0.08 ± 0.03 vs. 0.10 ± 0.04, p = 0.026; 0.31 ± 0.09 vs. 0.38 ± 0.11, p = 0.008. The thickness of retinal pigment epithelium (RPE) correlated positively with the choroidal vascularity index (CVI). The correlations between outer nuclear layer (ONL), photoreceptors (PR) and foveal choroidal thickness (FChT) were moderately negative. (4) Conclusion: Thicker RPE and a thinner PR layer may be assigned the role of early biomarkers signaling the conversion time to progressing retinopathy.

Optical Coherence Tomography Biomarkers of the Outer Blood-Retina Barrier in Patients with Diabetic Macular Oedema.

BACKGROUND: Numerous studies confirmed the main role of the inner blood-retinal barrier in the development of Diabetic Macular Oedema (DMO). Lately, the focus of research shifted towards the external retinal barrier with potential involvement in the pathogenesis of DMO. OBJECTIVE: We aim to identify the OCT changes of the external blood-retinal barrier in patients with DMO and to define them as biomarkers with predictive value. Materials and method. We set up retrospectively 3 groups of patients diagnosed with nonproliferative diabetic retinopathy (NPDR) and DMO, proliferative diabetic retinopathy (PDR) and DMO, and controls. We compared the RPE thickness in every quadrant between groups and performed correlations between best-corrected visual acuity (BCVA) and the thickness of the retinal layers. The Social Science Statistics platform was used for statistical tests. RESULTS: The NPDR-DMO group consisted of 18 eyes, the PDR-DMO group consisted of 19 eyes, and the control group included 36 eyes. In the PDR-DMO group, RPE thickness was decreased in almost all quadrants (p < 0.001); in the NPDR-DMO group, only the central minimum and central maximum values of the RPE thickness were significantly different from the control group. We did not find any strong correlation between BCVA and the thickness of the retinal layers. CONCLUSION: The thickness of the RPE layer is an OCT biomarker able to predict the functioning of the outer BRB. Eyes with PDR-DMO exhibited decreased thickness of the RPE layer in almost all quadrants, highlighting the degenerative changes occurring in a hypoxic environment. The thickness of a specific layer could not be identified as a biomarker to correlate significantly with BCVA, most likely because we did not analyze specific morphologic features, such as continuity and reflectivity. The analysis of the RPE thickness could clarify the unexplained decrease of BCVA and predict early the evolution of DR.

The Burden of Assessing Ocular Status of Children - Causes and Control.

Pediatric ocular diseases can be detectable through a comprehensive eye examination and most of them are preventable once they are discovered. There is a well known fact that children can have ocular pathology such as cataract, refractive errors, strabismus and amblyopia. In children, low vision can have a negative impact on their growth and development; therefore, any visual impairment must be detected as soon as possible to prevent amblyopia development.

Visual outcomes and prognostic factors following 23G vitrectomy for vitreous hemorrhage in eyes with proliferative diabetic retinopathy / Desfechos visuais e fatores prognósticos após vitrectomia 23G para hemorragia vítrea em olhos com retinopatia diabética proliferativa

ABSTRACT Purpose: We aimed to evaluate the factors influencing the visual gain following pars plana vitrectomy for vitreous hemorrhage in patients with proliferative diabetic retinopathy. Methods: A retrospective study was conducted on 172 eyes of 143 consecutive patients with diabetes mellitus between January 2012 and January 2018. Demographic data, ophthalmological findings, surgery details, and visual outcomes were gathered after consulting the patients' records. The main outcome measured was the improvement of best corrected visual acuity and the secondary outcomes measured were rebleeding and complications. Results: Best corrected visual acuity improved in 103 eyes (59.88%), worsened in 45 eyes (26.16%), and remained unchanged in 24 eyes (13.95%). Type 2 diabetes mellitus was significantly associated with better final best corrected visual acuity (p=0.0244). Previous treatment by pan-retinal laser photocoagulation or intravitreal bevacizumab determined better final best corrected visual acuity, but not significantly (p>0.05). Preoperative rubeosis iridis and neovascular glaucoma did not influence the outcomes. The lack of fibrovascular proliferation requiring dissection was a significant factor for better final best corrected visual acuity (p=0.0006). Rebleeding occurred in 37.1% of the eyes and it was not influenced by the antiplatelet drugs (p>0.05). Postoperative neovascular glaucoma was a negative prognostic factor (p=0.0037). Conclusion: The final best corrected visual acuity was influenced positively by type 2 diabetes mellitus and the absence of preoperative extensive fibrovascular proliferation and negatively by postoperative neovascular glaucoma.

RESUMO Objetivo: Avaliar os fatores que influenciam o ganho visual após vitrectomia via pars plana para hemorragia vítrea em pacientes com retinopatia diabética proliferativa. Métodos: Foi realizado um estudo retrospectivo de 172 olhos de 143 pacientes consecutivos com diabetes mellitus entre janeiro de 2012 e janeiro de 2018. Dados demográficos, achados oftalmológicos, detalhes da cirurgia e resultados visuais foram coletados através de consulta aos prontuários dos pacientes. A principal medida de desfecho foi o aumento da melhor acuidade visual corrigida e as medidas de desfecho secundário foram a recidiva da hemorragia e a ocorrência de complicações. Resultados: A melhor acuidade visual corrigida aumentou em 103 olhos (59,88%), diminuiu em 45 olhos (26,16%) e permaneceu inalterada em 24 olhos (13,95%). O diabetes mellitus tipo 2 foi significativamente associado a maiores valores finais da melhor acuidade visual corrigida (p=0,0244). O tratamento prévio por fotocoagulação panretiniana com laser ou bevacizumabe intravítreo determinou maiores valores da melhor acuidade visual final corrigida, mas não significativamente (p>0,05). A presença de rubeose iridiana pré-operatória ou de glaucoma neovascular não influenciou os desfechos. A ausência de proliferação fibrovascular com necessidade de dissecção foi um fator significativo para maiores valores da melhor acuidade visual final corrigida (p=0,0006). Ocorreu recidiva da hemorragia em 37,1% dos olhos e não foi influenciada por fármacos antiplaquetários (p>0,05). O glaucoma neovascular pós-operatório foi um fator prognóstico negativo (p=0,0037). Conclusão: O resultado final da melhor acuidade visual corrigida foi influenciado positivamente pelo diabetes mellitus tipo 2 e pela ausência de proliferação fibrovascular extensa no pré-operatório, e negativamente pela ocorrência de glaucoma neovascular pós-operatório.

[Cryptococcus meningitis, five years of experience and literature review]. / Meningita cu Cryptococcus spp. Cinci ani de experienta si revista literaturii.

UNLABELLED: The aim of this study was to determine the distribution and antifungal susceptibility profile of Cryptococcus spp. isolated from patients in northeast Romania. MATERIAL AND METHOD: Fungi isolated from blood and cerebrospinal fluid (CSF) cultures were identified by ID32C strips (bioMerieux, France). Susceptibility testing was performed using ATB FUNGUS2 strips (bioMerieux, France). RESULTS: A total of 20 significant strains have been isolated. Overall, Cryptococcus neoformans was the most frequent isolate (95%). We mention the first Cryptococcus albidus meningitis in Romania (strain with multiple resistance). All cryptococci tested were susceptible to amphotericin B with minimal inhibitory concentration (MIC) =1 microg/mL; 90% strains were susceptible to flucytosine. Resistance to fluconazole and itraconazole was observed in 2 and 1 case, respectively. Most of the patients had an associated infection, tuberculosis in 37.5% cases. Despite appropriate therapy 4 patients died (21%). CONCLUSION: First choice induction therapy with amphotericin B plus flucytosine followed by fluconazole is highly recommended since resistance to antifungal agents is still very low.